کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2142855 1088328 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Lipid raft modulation inhibits NSCLC cell migration through delocalization of the focal adhesion complex
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Lipid raft modulation inhibits NSCLC cell migration through delocalization of the focal adhesion complex
چکیده انگلیسی

Lipid raft, a specialized membrane structure enriched with cholesterol and glycosphingolipid, contains molecules that convey environmental stimuli to the intracellular systems. Authors investigated the effects of raft cholesterol depletion on non-small cell lung cancer (NSCLC) cell migration. Incubation of NSCLC cells in media containing lovastatin resulted in inhibition of cell migration by 63.1–83.3%, whereas raft cholesterol depletion with successive treatment using methyl-β cyclodextrin (MβCD) followed by lovastatin further suppressed their migration by 35.0–57.8%. Raft cholesterol depletion partially inhibited EGF-induced phosphorylation of EGFR and FAK, however, no change was observed in other molecules comprising focal adhesion complex. It resulted in disappearance of filopodia, inhibition of EGF-induced pY397 FAK aggregation, and its destabilization. Cholesterol depletion inhibited phosphorylation of Src on Y416 in the detergent-insoluble fraction followed by decreased localization of total and pY397 FAK in the detergent-insoluble fraction. Minimal changes in these molecules were observed in the detergent-soluble fraction and interactions between FAK and other molecules of the focal adhesion complex were not influenced. Immunocytochemical analysis confirmed translocation of Src from the raft into cytoplasm and disappearance of EGF-induced membrane ruffling by raft cholesterol depletion. In cholesterol-depleted cells, EGF-induced phosphorylation of Src, Akt, and p44/42 in the detergent-insoluble fraction were inhibited whereas phosphorylation of GSK-3β was unaffected. We conclude that raft cholesterol depletion inhibited NSCLC migration through inhibition of phosphorylation of raft associated Src and dislocation of molecules comprising focal adhesion complexes from raft rather than by inhibiting their recruitment to Src and interaction.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Lung Cancer - Volume 69, Issue 2, August 2010, Pages 165–171
نویسندگان
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